Appropriate Use of Recovery Groups in Nonclinical Toxicity Studies: Value in a Science-Driven Case-by-Case Approach

Abstract

A recovery phase—a nondosing period that follows the main dosing phase of a study—is sometimes included in nonclinical toxicity studies, and it is designed to understand whether toxicities observed at the end of the dosing phase are partially or completely reversible. For biopharmaceuticals with long half-lives, the inclusion of recovery arms can be helpful in understanding effects of prolonged exposure and assessing antidrug antibodies. This commentary discusses when to include recovery groups in nonclinical toxicity studies, the number of recovery groups to include in a given study, the number of animals to include in each recovery group, and the duration of the recovery phase. In general, the inclusion of recovery arms should follow a case-by-case approach that values rational scientific design and reflects the development needs and regulatory requirements applicable to individual nonclinical programs to ensure appropriate guidance for human studies while minimizing laboratory animal use.